黑皮质素-4 受体的激活促进了胰岛素刺激的 mTOR 信号通路。
Melanocortin-4 receptor activation promotes insulin-stimulated mTOR signaling.
机构信息
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
出版信息
Peptides. 2010 Oct;31(10):1888-93. doi: 10.1016/j.peptides.2010.06.028. Epub 2010 Jul 31.
The melanocortin signaling system is integral in regulating energy homeostasis. The melanocortin-4 receptor (MC4R) activates several signaling pathways in performance of this function. The effect of MC4R on insulin-stimulated mammalian target of rapamycin (mTOR), a cellular energy sensor, signaling was investigated. The GT1-1 cell line which expresses MC4R expression was utilized. mTOR signaling was measured by Western blotting analysis using Phospho-mTOR (Ser2448) antibody. NDP-MSH dose-dependently enhanced insulin-stimulated mTOR phosphorylation. The MC4R antagonist SHU9119 blocked this effect, demonstrating specificity. The protein kinase A - cyclic AMP pathway and the MAP kinase pathway were not involved in NDP-MSH actions on insulin-stimulated mTOR phosphorylation. In contrast, the AMP-activated protein kinase agonist, AICAR, attenuated this effect. MC4R activation potentiates insulin-stimulated mTOR signaling via the AMPK pathway.
黑素皮质素信号系统在调节能量平衡中起着重要作用。黑皮质素-4 受体（MC4R）在执行这一功能时激活了几个信号通路。研究了 MC4R 对胰岛素刺激的哺乳动物雷帕霉素靶蛋白（mTOR）的影响，mTOR 是一种细胞能量传感器。利用表达 MC4R 的 GT1-1 细胞系进行 mTOR 信号的 Western blot 分析，用磷酸化 mTOR（Ser2448）抗体测量。NDP-MSH 呈剂量依赖性增强胰岛素刺激的 mTOR 磷酸化。MC4R 拮抗剂 SHU9119 阻断了这种作用，表明其具有特异性。蛋白激酶 A - 环腺苷酸途径和 MAP 激酶途径不参与 NDP-MSH 对胰岛素刺激的 mTOR 磷酸化的作用。相反，AMP 激活的蛋白激酶激动剂 AICAR 减弱了这种作用。MC4R 的激活通过 AMPK 途径增强了胰岛素刺激的 mTOR 信号。
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